Aggression is a nearly universal feature of the behavior of social animals. In the wild, it is used for access to food and shelter, for protection from predation and for selection of mates. Despite its importance, little is known of the neural mechanisms that underlie the behavior. In this proposal a genetic approach will be taken to the examination of aggression using the fruit fly, Drosophila melanogaster, as the experimental model. With the genome sequenced, with a wealth of powerful genetic methods available, and with the recognition that similar genes are used in similar ways in all species of animals, including humans, studies with fruit flies should yield important information towards understanding this complex pattern of behavior. The long-term goals of the present studies are to identify genes and molecules, subtypes of neurons, and neuronal pathways important in aggression in fruit flies. Towards these goals, this application has four Specific Aims. I. Behavioral studies will address the questions: (1) Do females fight and can their behavior be analyzed; and (2) Are there long- and/or short-term memories of social status as a consequence of winning or losing fights. II. Amines like serotonin have been implicated in aggression in most species of animals. Mutant fly lines will be generated in which amine neuron function can be turned off and on in the brain by small changes in temperature. The powerful GAL4/UAS system will be used for this purpose, and we will selectively modify the function of serotonin, dopamine and octopamine neurons to observe the effects on fighting behavior. III. Assuming that as in most species, there will be a memory of social status: (1) fighting behavior will be examined in flies in which mushroom bodies (brain areas important in memory in flies) have been chemically ablated; (2) fighting behavior will be examined in learning mutant fly lines; and (3) GAL4 lines will be used to examine the effects on fighting behavior of reversibly ablating subsets of mushroom body neurons. IV. Parkinson's and Alzheimer's/Frontotemporal Dementia disease models have been generated in flies by creating transgenic animals with proteins known to be involved in these diseases in humans. One phenotype associated with these disorders is enhanced aggression. The fly models will be examined to see if they too show enhanced aggression. [unreadable] [unreadable]